Leucine ingestion promotes mTOR translocation to the periphery and enhances total and peripheral RPS6 phosphorylation in human skeletal muscle.
Level 4 - case-series / case-control
Single-arm uncontrolled pre-post experimental study in humans
PubMed 36474017 · doi:10.1007/s00726-022-03221-w
What was done
Eight healthy, recreationally active young men (age 23 ± 3 years) ingested 2 g of free leucine. Vastus lateralis muscle biopsies were obtained at baseline, 30, 60, and 180 minutes postprandial. Immunofluorescence analysis assessed intracellular translocation of mTOR to the cell periphery and lysosome, alongside total and peripheral phosphorylation of ribosomal protein S6 (p-RPS6 Ser240/244), which was correlated with myofibrillar protein synthesis rates measured over 180 minutes.
What was found
Leucine ingestion increased mTOR translocation to the cell periphery by ~18% to 29% (p ≤ 0.012) and enhanced lysosomal colocalization by ~16% (both p = 0.049) at 30 and 60 minutes. p-RPS6 Ser240/244 staining intensity increased across all postprandial timepoints in both total fiber (~14% to 30%, p ≤ 0.032) and peripheral regions (~16% to 33%, p ≤ 0.014). At 60 minutes, total and peripheral p-RPS6 intensities positively correlated with myofibrillar protein synthesis rates over 180 minutes (r = 0.74, p = 0.036 and r = 0.80, p = 0.016, respectively).
Why it matters
This study provides human spatial evidence that isolated leucine stimulates mTORC1 translocation toward the muscle cell periphery and lysosome, linking spatial mTORC1 activation to postprandial myofibrillar protein synthesis.
Limits
The sample size was very small (n = 8) and restricted entirely to young, healthy, recreationally active males, limiting generalizability to females, older adults, or clinical populations. There was no placebo or isonitrogenous control group to isolate leucine's specific effect from non-specific meal or time-course artifacts.
Cited by
- supports Consuming red meat, lamb, and eggs stimulates the mTOR pathway due to specific amino acids they contain.